Human bronchus, colon, duodenum, esophagus, and pancreatic duct cultured either as explants or epithelial cells in chemically defined media provide an excellent in vitro system to study the metabolism of chemical carcinogens, including those found in tobacco smoke and the environment. Several classes of chemical carcinogens, polynuclear aromatic hydrocarbons, N-nitrosamines, hydrazines, aromatic amines, and mycotoxins, can be metabolically activated by human tissues. Fetal human liver, stomach, and esophagus cultured as explants metabolized the same group of compounds. The metabolic pathways leading to the formation of DNA adducts in explants and epithelial cell cultures have been defined for benzo[a]pyrene (BP), 7,12-dimethylbenz[a]anthracene, aflatoxin B1 (AFB), and N,N-dimethylnitrosamine (DMN). The adducts between these carcinogens and DNA in human tissues are essentially the same as those found in experimental animals in which the chemicals are carcinogenic. Interindividual differences in carcinogen-DNA binding values vary 50- to 150-fold. The role of AFB in liver carcinogenesis has been further studied. We found that when urine samples collected in Kenya were analyzed for the presence of 2,3-dihydro-2-(7'-guanyl)-3-hydroaflatoxin B1 (AFB-Gua I) by high pressure liquid chromatography, 11 of 128 samples had a detectable level of AFB-Gua I; its identity was confirmed by photon-counting fluorescence spectrophotometry. The positive samples were primarily from people living in low-lying areas and collected in the rainy season when AFB contamination of the food is highest.